PROJECT SUMMARY/ABSTRACT This project addresses the epidemiological observation of increasing rates of obesity and type-2 diabetes mellitus (T2DM) across generations of Hispanic Americans. We propose a novel hypothesis to understand this phenomenon based on the concepts of fetal programming, social determinants of health, and biological embedding of life experience. Evidence suggests that the embryonic/fetal phase of life represents a critical window during which perturbations in the intrauterine biochemical environment affect development of body tissue patterning and metabolic function, influencing an individual?s lifelong health and susceptibility to obesity and T2DM. We posit that social and cultural stressors among Hispanic immigrant women may influence stress biology in ways that?for women who become pregnant?alter the biochemical environment to which the developing embryo/fetus is exposed. Hispanic immigrants are an exceptionally disadvantaged group who are vulnerable to high degrees of social adversity. We propose the original hypothesis that pregnant, Hispanic immigrant women?s perceived social adversity may alter stress-related biological processes to influence adiposity and metabolic phenotypes in the fetus, thereby pre-disposing the offspring to enhanced lifelong risk of obesity and T2DM. In a prospective, longitudinal study of 100 pregnant, Hispanic immigrant women established with the PI?s K-award, we will assess perceived social adversity from a series of original open-ended questions, Likert-scale items, and validated questionnaires, and relate these constructs to stress biology assessed from biosamples collected at two timepoints during pregnancy, and newborn body mass index percentiles (BMIP). Newborn body size has well-established correlations with childhood and adulthood adiposity and metabolic risk. In this context, we will pursue two specific aims. In Aim 1, we will examine how pregnant women?s perceived social adversity (immigration-related trauma, political victimization, discrimination) relates to four domains of gestational stress physiology: hypothalamic-pituitary-adrenal-placental, inflammatory, metabolic, and oxidative. In Aim 2, we will examine how pregnant women?s perceived social adversity relates to newborn BMIP. The expertise the PI gained in theory and analytic techniques for socio-cultural constructs, maternal-placental-fetal biology, adiposity and metabolism in her K01 training and research make her uniquely suited to successfully execute the R03 aims. Her K01 project, which focused on the possibility that acculturation may influence gestational biology, is logically extended in this R03 proposal by assessing other dimensions of socio-cultural stress, characterizing gestational stress physiology more comprehensively, and, importantly, directly measuring child outcomes. These endeavors will lay the foundation for an R01 proposal that will establish the PI as a fully independent investigator. Ultimately, these analyses may reveal new information about how experiences of social adversity can promote chronic disease states not only in the afflicted individuals but also across generations. Understanding the interplay between social, cultural, and biological mechanisms in minority health disparities may reveal new social, cultural, or biological targets of intervention to diminish inter-generational cycles of disadvantage and poor health in minority communities. This project emphasizes the possibility that investment in the well-being of girls and women can help alleviate health disparities.